The usual flora in the urogenital region is constituted by a complex ecosystem comprising more than 50 different bacterial species (Hill et al., Scand. J. Urol. Nephrol. 1984(86 (suppl.)):23-29). The normal flora is dominated by bacteria belonging to the genus Lactobacillus (LB) which are Gram positive rods adapted to the environment in the vagina of the fertile woman. These bacteria also contribute to the maintenance of the specific milieu and the ecological balance in the vagina. The surrounding pH in the vagina is lower than 4.5. Yeast and enterobacteria are scanty or absent (Redondo-Lopez et al, Rev. Inf. Dis. 1990(12):856-872).
Some LB strains inhibit growth of potentially pathogenic bacteria by various mechanisms. The metabolism of LB results in formation of organic acids, in particular lactic acid and acetic acid, which contribute to the low pH of vaginal fluid, which is unfavorable for many other microbial species. LB may also produce soluble substances which directly inhibit growth of potentially pathogenic bacteria and yeast. They can also produce hydrogen peroxides, which is toxic to bacteria and fungi. These inhibiting characteristics may vary considerably between different LB strains (Hooton et al., JAMA 1991(265):64-69).
Similarly to the urogenital area, the skin is colonized by an array of organisms, which forms its normal flora. The numbers and identity of the organisms vary between different skin sites, with moist and lipid skin areas harbouring more microorganisms per skin area. This, together with the skin's structural barrier, provides the host with an excellent defense against invading microbes. The number of bacteria on the skin varies from a few hundred per cm2 on the arid surfaces of the forearm and back, to tens of thousands per cm2 on the moist areas such as the axilla and groin. This normal flora plays an important role in preventing ‘foreign’ organisms from colonizing the skin, but it to needs to be kept in check, in order to avoid skin infections.
The gastro intestinal (GI) tract, from mouth to anus, harbors a rich flora of more than 500 different bacterial species, some of which have important health functions. The GI flora consists of about 1014 bacteria and a low number of commensally yeast. Due to a changed general health state, Candida species may overgrow and cause superficial infections. Furthermore, overgrowth of Candida species among immunocompromised patients can lead to a systemic infection which is a very serious condition.
Weakness of or imbalance in the natural defense system may allow potentially pathogenic micro-organisms to cause clinical infection, for example in connection with medication, inferior personal care, or shifts in the microflora or mucous membranes. Shifts in the micro-flora can also be found in connection with different pathogenic conditions.
Yeast organisms are always present in humans, but are usually prevented from overgrowth by the indigenous microbial flora. Candidiasis is an infection caused by Candida yeast organisms that affects a wide variety of organ systems. Most commonly, the infection is caused by Candida albicans, and C. glabrata. Less commonly, C. tropicalis, C. parapsilosis, and C. kruseii cause the infection and rarely, other Candida species are the causative agent. Candidiasis is often triggered by hormonal changes, such as during pregnancy, menstruation and the use of birth control pills. Other common causes are imbalances in the pH in the vagina, diabetes mellitus, and antibiotic cures, disturbing the delicate microbiological balance of the body. The natural host defense against Candida infections include mechanical barriers, non-specific antimicrobial substances (polypeptides, basic proteases), phagocytosis, and specific immune response (T- and B-lymphocytes, delayed-type hypersensitivity.
In immunocompetent persons, any warm, moist part of the body exposed to the environment is susceptible to infection causing vaginitis; vulvar rash; oral thrush; conjunctivitis; endophthalmitis; diaper rash; and infections of the nail, rectum, and other skin folds. In immunocompromised patients, systemic illnesses such as myocarditis, hepatosplenic abscess, pulmonary infection, CNS infection, and chronic disease may occur. Candidiasis may spread from a local infection to cause a systemic infection with serious complications, such as myocarditis, endophthalmitis and hepatosplenic abscess. It is therefore of great importance to find effective cures and preventive treatments for candidiasis, to avoid this serious condition in subjects.
Thrush is the common name for a mouth infection caused by the Candida albicans fungus that affects moist surfaces around the lips, inside the cheeks, and on the tongue and palate. Thrush is common in people with diabetes or irritation from dentures. Also people with diseases such as cancer and AIDS, which both suppress the immune system, are often affected by candidiasis.
A Candida infection of the mouth can spread to the esophagus, causing esophagitis. This infection is most common in people with AIDS and people receiving chemotherapy for cancer.
Candida infection are also common on moist skin parts, such as skin areas covered by diapers, the hands of people who routinely wear rubber gloves, the rim of skin at the base of the fingernail, especially for hands that are exposed to moisture, areas around the groin and in the crease of the buttocks, and the skin folds under large breasts.
Vaginitis is an inflammation of the vaginal mucosa caused by bacteria or fungi. Vaginitis is in itself initially harmless but can lead to premature birth in pregnant women or infertility.
Vaginal candidiasis causes an itching and irritated vagina with whitish, limpy discharge that may resemble cottage cheese. It is often very discomforting for the woman experiencing the symptoms and in addition causes restrictions to normal activities, such as sport exercises and sexual activity.
Vaginal candidiasis is normally treated locally by creams, suppositories, gelatin capsules, vaginal tablets and ointments comprising antifungal agents. Orally administered cures are also available. One problem with antifungal agents is an increased resistance of the fungus to the agent if used repeatedly. In addition, such cures are often inefficient and require a doctor's prescription.
Home remedies, such as application of yoghurt, acidophilus tablets or vinegar douches are also used for treating candidiasis. However, the efficiency of these treatments has been low. Although yoghurt comprises lactobacilli, these are not especially adapted for killing or reducing the growth of fungi. As is understood by the person skilled in the art, such a treatment can only be effective to mitigate the symptoms of minor infections. It has also been suggested that lactic acid producing bacteria can be delivered via absorbent articles, such as diapers, sanitary napkins, panty liners and tampons, as described in e.g. W097/02846, WO99117813, WO99/45099 and WO00/35502.
There is an increasing interest in finding probiotic microorganisms being able to restore a healthy microbial flora and/or prevent the uncontrolled growth of unwanted microorganisms. Administration of such probiotic bacteria do not have the negative side effects of antifungal agents and preferably are more efficient in the treatment and/or prevention of fungal infections. Previous attempts to find such microorganisms have had various successes though, due to problems such as low attachment and survival of the probiotics in the vagina, limited efficiency in the prevention of fungal growth, low survival during storage of the preparations etc. Other important features of a selected probiotic is ability to grow in the presence of oxygen and survive freeze-drying. Most importantly though, the probiotic bacterium selected must be efficient in the killing and/or prevention of growth of unwanted fungi and/or bacteria. Probiotic lactobacilli have previously been proven efficient in the treatment and prevention of bacterial vaginitis. However, success in the prevention and/or treatment of vaginal candidiasis has been very limited. Therefore, there is still a need for the development of efficient probiotics for the treatment of candidiasis, including vaginal candidiasis, that also may be effective against bacterial infections, such as urinary tract infections.